Systemic lupus erythematosus (SLE) is a disease that has been investigated in human as well as in murine models. In both species, the disease is associated with multiple abnormalities of the immune system regulation. Impaired T cell functions combined with spontaneous B cell hyper-reactivity result in uncontrolled formation of autoantibodies. The early immunologic events that trigger the disease, on the background of well-documented genetic predisposition, are not fully understood. Most of the immune abnormalities in SLE have been correlated with disease activity and therefore may be results of the disease rather than causes. We have described a severe impairment in the production of the cytokines Interleukin-1 (Il-1) and Interleukin-2 (Il-2) in SLE patients, that did not correlate with disease activity. Both cytokines are necessary for the development of normal T cell and B cell responses. Impaired II-1 and II-2 production may represent early defects that would be responsible for some of the immune disorders in SLE. We hope (1) to learn the mechanisms that cause the defective production of II-1 and II-2 in patients by studying the producer cells, their interaction with accessory cells and modulating endogenous factors, and the pattern of production of II-1 and II-2 in families of SLE. (2) To test the hypothesis that subpopulations of T cells vary in their requirements of lymphokines, and that the lower II-2 levels in SLE will preferentially select for T helper cells while T suppressor function will be lost. (3) To devise in vitro systems for reconstitution of the defective production of II-1 and II-2 and to study the effects such a reconstitution will have on the production of antibodies in SLE.